Presentation Group 5

Emmanuel, Adomas, Subhayan and Chuang

Introduction

Hidradenitis suppurativa (HS) is a common, debilitating inflammatory skin disease linked to immune dysregulation and abnormalities in follicular structure and function. The study we looked at tries to derive an expression-based HS disease signature by observing affected and unaffected skin from 20 subjects and characterize a transcriptomic profile through RNASeq. Differential expression and pathway enrichment analyses were then performed, and the results were compared to previously reported datasets.


We obtained the RNASeq data used for the study - A Hidradenitis Suppurativa Molecular Disease Signature Derived from Patient Samples by High-Throughput RNA Sequencing, available on GEO RNASeq results for 40 samples - and tried to replicate the differential expression profiling and pathway enrichment analyses.

Trace the Flow of the Project

Load

We read the data from GSE151243

# Loading the data
path_gene = "../data/_raw/GSE151243_Raw_gene_counts_matrix.txt"
path_meta = "../data/_raw/GSE151243_series_matrix.txt"
gene_table <- read.table(path_gene, header = TRUE)
meta_table <- read.table(path_meta, skip = 33, fill = TRUE, header = TRUE)

Data Cleaning

  • Start with 58051 genes in the pool
    1. Remove gene if 0 expression for all patients (-6098)
    2. Remove gene if expression linear model coefficient not significant between diseased/healthy tissue (p>0.05) (-51437)
    3. Remove gene if expression change for all patients < 3-fold between the diseased/healthy tissue groups ( -29)
  • 487 genes advance to analysis rounds

Materials and Methods

Results

Principal Component Analysis

Score Plot

Variance Explained

Most Upregulated and Downregulated Genes

Functional Assessment of Upregulated and Downregulated Genes

  • Upregulated genes:
    • NTRK1: Neuronal survival and Signal Transduction\n(MAPK, PI3K-Akt, PLC-\(\gamma\))
    • POU2AF1: B-Cell immune responds
    • SIGLEC7: Inhibition of NK-Cell responds
  • Downregulated genes:
    • KRT77: Kreatin, Intermediate filament protein
    • CHRM1: Muscarinic receptor
    • PHYHIP: Fatty acid metabolism and perioxisomal function

Enhanced Activation of Inflammatory, Innate and Adaptive immune pathway

Reduced Activity in Hair, Skin and Neural Cell Division Pathways

Discussion

  • Observations by Freudenberg et al.
    • Gene Upregulation
      • MMP1, C-X-C, SERPINB4, and S100.
    • Enhanced Immune Responses
      • Upregulation in both adaptive and innate immune system functions.
    • Reduced Keratinization and Intermediate Filament Activity
  • Potential Causes for Variance in Results
    • Model Selection
      • lm vs glm, Empirical Bayes
    • Adjusted P-value Cutoff Choices
    • Gene Selection Criteria
      • Focus only on protein-encoding genes

Chromosome Distribution of Upregulated genes

Chromosome Distribution of Downregulated genes

Read Counts are higher for Raw genes

Some nonlesional samples have higher read counts of Significant genes